An international team of researchers, including Miller School pulmonologist Marilyn K. Glassberg, M.D., has confirmed the results of earlier trials that pirfenidone, a medication already approved for use in nearly three dozen countries, is effective in slowing the progress of idiopathic pulmonary fibrosis. Their findings were published in the May 20 issue of The New England Journal of Medicine.

Glassberg, professor of medicine and surgery, Director of the Interstitial and Rare Lung Disease Program and Director of the Pulmonary Division at the Interdisciplinary Stem Cell Institute, collaborated with researchers at 126 other sites in nine countries in the large, phase 3 trial, which involved a total of 555 patients. She was also part of the trial’s steering committee.

Idiopathic pulmonary fibrosis (IPF) is a disease in which tissue in the lungs becomes thickened and stiff, or scarred, for no apparent reason. As the lungs stiffen, they gradually lose their ability to pump oxygen into the bloodstream, resulting in reduced levels of oxygen reaching the brain and other organs. The progressive disease most commonly affects middle-aged and older adults, mostly males, and it is irreversible and has no cure.

“There are approximately 100,000 cases in the U.S. in any given year,” said Glassberg, noting that IPF is five times more common than cystic fibrosis. “The biggest risk factor is having ever been a smoker. Our all-cause mortality rate was 6.6 percent at one year and 13.7 percent at two years. That’s relatively low, but our study only included patients with mild-to-moderate disease. The rate would be higher with severe cases, but these patients tend to present too late for any potential therapeutic intervention. The severe cases were not part of this study.”

Three earlier trials had been conducted — one in Japan and two multinational trials in the U.S., Europe and Australia. The multinational trials, known as CAPACITY 004 and CAPACITY 006, involved a total of 779 patients. Glassberg’s Miami site was the highest enroller of subjects. The results from the CAPACITY trials were encouraging and led to the commercialization of pirfenidone in 35 countries. The U.S. Food & Drug Administration, however, requested an additional trial based on an unexplained statistical inconsistency between the two CAPACITY trials.

“Basically, the baseline characteristics in the two CAPACITY studies showed a greater proportion of placebo patients in study 006 had less decline in lung function,” said Glassberg.

The follow-up trial — called ASCEND — left no doubt about the drug’s positive impact. In the most significant finding, at 52 weeks nearly half of the patients taking the drug exhibited less lung volume lost, as measured by forced vital capacity (FVC), than in those taking the placebo. That means the disease had slowed down in those patients taking the drug, said Glassberg.

“To reduce the incidence of a decline in FVC by almost 200cc amounts to 10 percentage points and fewer deaths at one year compared with the placebo. That’s a huge impact,” said Glassberg. “I don’t think anyone involved in the study ever expected numbers like that.”

There also were important secondary indicators at 52 weeks. The exercise tolerance portion — a walk test — showed a 27.5 percent reduction in decline in patients taking pirfenidone when compared with those taking the placebo. The drug also reduced the risk of death or disease progression by 43 percent compared with the placebo.

In addition, said the study report, when the CAPACITY and ASCEND trials were combined — a total of 1,334 subjects — the data across the larger patient pool matched closely, eliminating the statistical anomaly that had concerned the FDA.

“This isn’t a cure,” cautioned Glassberg, “but we have shown we can slow the disease and reduce the death rate. That is a major push forward in the field.”

The next step, she said, is going to be stem cell research to see if it is possible to stop the disease progression completely. Scientists already know they can’t reverse it.

“Unlike other organs, the lungs do not regenerate,” said Glassberg, “but stem cells have had a tremendous impact in other fields, such as cardiology, so we want to study their possible impact.”

Even if researchers don’t have a cure yet for IPF, they are learning a lot about the disease, and more studies are planned.

“IPF has become a hot area for research,” said Glassberg, “and there are lots of new drugs in the works. The goal for the pulmonary world is to cure this disease.”